The era of modern pharmacology has ushered in a wealth of drugs that selectively modulate molecular systems within cells, tissues and organs. However, despite the sheer number of drugs/drug classes now available, very few pharmacological agents are known to be effective in organ preservation solutions.
The identification of drugs that preserve organs has enormous implications for progress in medicine. For example, effective drugs that can be added to organ preservation solutions, such as University of Wisconsin solution, Celsior solution, St. Thomas Hospital 2 solution, Ringer-lactate solution, Euro-Collins solution or Bretschneider HTK solution could extend the time for extracorporeal survival of grafts prior to transplantation, decrease the incidence of primary graft dysfunction and delayed function and augment the pool of available donors. Preserving drugs could be delivered to the organ while still in the donor (in situ) or instilled into the organ after removal from the donor (in vitro). In addition to or instead of adding preserving drugs to a preservation solution, the drugs may be administered to the organ donor before removal of the organ (in vivo) or to the organ recipient (in vivo) before or just after transplant. Moreover, such drugs may find utility for the prevention and treatment of acute organ failure, for example acute renal failure for which no effective pharmacological agent is currently known. Furthermore, protecting drugs, if sufficiently efficacious, may allow for the prolonged in situ perfusion of organ systems with solutions to restore organ function and/or to selectively deliver other drugs or molecular biological constructs (e.g., plasmids, viral vectors, siRNAs, anti-sense oligonucleotides) directly to the target organ.
Accordingly, there is a desire in the art for methods and compositions for reducing, preventing or reversing organ damage or enhancing organ preservation.